褪黑素抑制雌二醇诱致的垂体PRL瘤生长与血浆PRL和过氧化脂质含量的关系

Inhibitory effects of melatonin on the developmen of 17-β-estradiol induced prolactinoma in relation to plasma prolactin and peroxidative lipid contents

雄性Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠皮下埋置１７－β雌二醇（１７－β－ｅｓｔｒａｄｉｏｌ，Ｅ２）药泵诱发垂体催乳素（ｐｒｏｌａｃｔｉｎ，ＰＲＬ）瘤，并每日皮下注射褪黑素（ｍｅｌａｔｏｎｉｎ，ＭＬＴ），观察ＭＬＴ对Ｅ２诱发ＰＲＬ瘤生长的影响。另外，采用放免法和紫外分光光度法测定大鼠血浆ＰＲＬ和过氧化脂质（ｐｅｒｏｘｉｄａｔｉｖｅ ｌｉｐｉｄ，ＰＬ）浓度，观察ＰＲＬ瘤重量与大鼠血浆 ＰＲＬ、ＰＬ浓度间的相关关系。实验结果显示，在对照组、０．０５、０．２５、０．５０、１．００和 ２．００ｍｇ ＭＬＴ组，ＰＲＬ瘤重量分别为１１５．０±７１．０、８５．２±４１．０、５８．９±２４．１、７２．７±２３．６、７９．３±５６．１、７４．５±４６．８ｍｇ；血浆ＰＲＬ浓度分别为４９３．４６±３３．３、３７３．７８±２６．５、１２５．１３±１３．３、２０１．７９±１１．２、４１８．８８±４１．３、２８１．９４±３６．４ｎｇ／ｍｌ；血浆ＰＬ水平分别为１．２１±０．２３、０．８９±０．３２、０．９２±０．２７、０．６４±０．２４、０．４１±０．１４、０．４３±０．２１△Ｄ２３３／ｍｌ。相关性分析表明，ＰＲＬ瘤重量与血浆 ＰＲＬ浓度间的相?

In the present study, we have examined inhibitory effects of melatonin on the development of pi- tuitary prolactin-producing tumors (prolactinorna) induced by 17-β-estradiol (E2) in vivo.The prolactinomas were established by implanting E2-laden silastic capsules subcutaneously in Sprague-Dawley male rats weighing 80-100g. Melatonin (0.05, 0.25, 0.50, 1.00, and 2.00 mg/0.1 ml/rat) was administrated subcuta- neously at 18:00 h for 90 days, beginning from d 7 prior to tumor induction. Controls were given equal vol- umes of 4% alcohol in 0.9% saline. Our results showed: (1) In control group and groups given respectively 0.05, 0.25, 0.50, 1.00 and 2.00mg melatonin, the weight of prolactinoma was 115.0 ± 71.0, 85.2± 41.0,58.9±24.1, 72.7±23.6, 79.3±56.1, 74.5±4.6.8 mg respectively; the plasma prolactin (PRL) contentwas493.46±33.3, 373.78±26.5, 125.13±13.3, 201.79±11.2,418.88±41.3,281.94±36.4 ng/ml respectively; the plasma peroxidative lipid content was 1.21± 0.23,0.89 ± 0.32,0.92 ± 0.27, 0.64 ± 0.24, 0.41± 0.14 and 0.43 ± 0.21 △D233/ml respectively. (2) The correlation coefficients between tumor weight and plasma PRL content, tumor weight and plasma peroxydatiove lipid content, and plasma PRL content and plasma peroxydative lipid content were 0.8738, 0.5550 and 0.2141 respectively. These results indicate: (1) The dosages of 0.25 (P<0.01) and 0.50(P<0.05) mg, but not 0.05 (P>0.05), 1.00 (P >0.05) and 2.00 (P > 0.05) mg, melatonin significantly inhibited the development of the E2-induced prolactinoma and the secretion of PRI in comparison with the matched control. (2) The levels of 0.05~2.00 (P <0.05~0.001) mg melatonin showed a dose-dependent antioxidative action. (3) There are positive correlation between tumor weight and plasma PRL content (P <0.05), but no correlation between tumor weight and plasma peroxidative lipid content (P > 0.05), and plasma PRL content and plasma peroxidative lipid content (P > 0.05). Therefore, our experiments demonstrate that the inhibition of the development of E2-in-duced prolactinoma by adequate dosage of melatonin may be related to the inhibitory effects of MLT on the se-cretion of PRL, but not to the antioxidative action of MLT.